ANTIGENIC DETERMINANTS OF VARICELLA VIRUS

水痘-带状疱疹病毒(VZV)是一种人类疱疹病毒。 儿童常见疾病水痘的病原体和 重新激活，皮肤瘤带状疱疹(带状疱疹)。虽然 对于健康的人来说，这两种疾病都很重要，只有适度的痛苦。 儿童和青壮年癌症患者的发病和死亡原因 或其他慢性疾病正在接受强化化疗或 骨髓/器官移植。因为VZV的严重后遗症 免疫低下患者中的感染，NIH-NIAID目前 赞助活体减毒VZV的合作临床试验 疫苗。这项赠款提案的目标是定义和描述 VZV的主要抗原决定簇。VZV指定的糖蛋白将是 被认为是自研究其他包膜病毒以来最优先的 证明糖基化抗原在 诱导保护性体液免疫和细胞免疫应答 受感染的宿主；相同的糖蛋白也介导早期事件 病毒与细胞的相互作用。具体目标包括 主要研究内容如下：(1)制备小鼠单抗 实验室指定的糖蛋白抗体和VZV疫苗 株系，(2)鉴定VZV的前体和成熟糖基化成分 感染细胞和被包裹的病毒粒子的合成，(3)研究合成， 病毒糖蛋白的加工和胞内转运，(4) 分离纯化单个病毒糖蛋白并进行 蛋白质和糖基的结构分析，以及(5)相互关系 生物学功能，如中和，抗体依赖细胞介导 细胞毒性和迟发型超敏反应及其决定因素 单独的糖蛋白。技术将包括放射免疫 沉淀、SDS-PAGE、免疫印迹、亲和和高效 高效液相色谱、胰蛋白酶多肽图谱、生物凝胶过滤 糖肽、碳水化合物的甲基化分析和免疫电子 显微镜。因此，这个研究项目将检验生物学， VZV糖蛋白的生物化学和免疫生物化学。在……里面 一项合作研究的努力，编码 将通过重组DNA技术绘制单个病毒糖蛋白的图谱。

Varicella-zoster virus (VZV) is the human herpesvirus which is the etiologic agent of both the common childhood illness chickenpox and, upon reactivation, the dermatomal exanthem shingles (herpes zoster). Although only moderately distressful in healthy people, both diseases are important causes of morbidity and mortality in children and young adults with cancer or other chronic illnesses being treated with intensive chemotherapy or bone marrow/organ transplantation. Because of the serious sequelae of VZV infection in immunocompromised patients, the NIH-NIAID is currently sponsoring a collaborative clinical trial of a live attenuated VZV vaccine. The goal of this grant proposal is to define and characterize major VZV antigenic determinants. Glycoproteins specified by VZV will be given the highest priority since studies of other enveloped viruses demonstrate that glycosylated antigens play an important role in the induction of protective humoral and cell-mediated immune responses by the infected host; the same glycoproteins also mediate early events in the interaction between virus and cell. The specific aims include the following investigations: (1) produce panels of murine monoclonal antibodies to glycoproteins specified by a laboratory and a vaccine VZV strain, (2) identify the precursor and mature VZV glycosylated constituents of the infected cell and the enveloped virion, (3) study the synthesis, processing and intracellular transport of the viral glycoproteins, (4) isolate and purify the individual viral glycoproteins and perform structural analysis of the protein and sugar moieties, and (5) correlate biologic functions, e.g., neutralization, antibody dependent cell mediated cytotoxicity and delayed type hypersensitivity with determinants on individual glycoproteins. Techniques will include radioimmune precipitation, SDS-PAGE, immunoblotting, affinity and high performance liquid chromatography, tryptic peptide mapping, Bio-Gel filtration of glycopeptides, methylation analyses of carbohydrates and immunoelectron microscopy. This research project, therefore, will examine the biology, the biochemistry, and the immunobiochemistry of the VZV glycoproteins. In a collaborative research endeavor, the structural genes which encode the individual viral glycoproteins will be mapped by recombinant DNA technology.